GB2620876A - Process for the preparation of drospirenone as a fine powder through a double change of crystalline form - Google Patents
Process for the preparation of drospirenone as a fine powder through a double change of crystalline form Download PDFInfo
- Publication number
- GB2620876A GB2620876A GB2316616.8A GB202316616A GB2620876A GB 2620876 A GB2620876 A GB 2620876A GB 202316616 A GB202316616 A GB 202316616A GB 2620876 A GB2620876 A GB 2620876A
- Authority
- GB
- United Kingdom
- Prior art keywords
- crystalline form
- drospirenone
- process according
- carried out
- suspension
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract 21
- METQSPRSQINEEU-UHFFFAOYSA-N dihydrospirorenone Natural products CC12CCC(C3(CCC(=O)C=C3C3CC33)C)C3C1C1CC1C21CCC(=O)O1 METQSPRSQINEEU-UHFFFAOYSA-N 0.000 title claims abstract 10
- METQSPRSQINEEU-HXCATZOESA-N drospirenone Chemical compound C([C@]12[C@H]3C[C@H]3[C@H]3[C@H]4[C@@H]([C@]5(CCC(=O)C=C5[C@@H]5C[C@@H]54)C)CC[C@@]31C)CC(=O)O2 METQSPRSQINEEU-HXCATZOESA-N 0.000 title claims abstract 10
- 229960004845 drospirenone Drugs 0.000 title claims abstract 10
- 239000000843 powder Substances 0.000 title claims abstract 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 6
- 239000000725 suspension Substances 0.000 claims 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims 4
- 238000001816 cooling Methods 0.000 claims 2
- 239000010419 fine particle Substances 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 238000000634 powder X-ray diffraction Methods 0.000 claims 2
- 239000007787 solid Substances 0.000 claims 2
- 238000001228 spectrum Methods 0.000 claims 2
- 238000003756 stirring Methods 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000013078 crystal Substances 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- 238000001914 filtration Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- 230000002269 spontaneous effect Effects 0.000 claims 1
- 230000009466 transformation Effects 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
- C07J53/002—Carbocyclic rings fused
- C07J53/004—3 membered carbocyclic rings
- C07J53/008—3 membered carbocyclic rings in position 15/16
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention refers to a process for the industrial-scale preparation of 17β-hydroxy- 6β,7β;15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21-carboxylic acid y-lactone, known by the common name of Drospirenone, in the form of a fine powder without the use of mechanical grinding or micronization techniques, but rather exploiting a double change of crystalline form, from Crystalline Form I to Crystalline Form II and from Crystalline Form II to Crystalline Form I. The invention also refers to the new Crystalline Form II of Drospirenone obtained in the process.
Claims (11)
1. Process for the production of 17P-hydroxy-6p,7P;15p,16P-dimethylene-3-oxo-17a- pregn-4-ene-21 -carboxylic acid g-lactone (Drospirenone) having fine particle size, characterized by a X90 value lower than 50 pm, through a double change of crystalline form: 1) from Crystalline Form I to Crystalline Form II, characterized by the presence in an XRPD spectrum of peaks at angles of 8.90°, 16.75° and 18.56° ± 0.2° 20; and 2) from Crystalline Form II to Crystalline Form I, characterized by the presence in an XRPD spectrum of peaks at angles of 12.30° and 17.35° ± 0.2° 20.
2. Process according to claim 1), comprising the following steps: a) preparing a suspension of a solid form of Drospirenone Crystalline Form I in a mixture of acetone and diisopropyl ether; b) cooling the suspension to a temperature equal to or lower than -5 °C; c) stirring the suspension at the temperature of point b) until the formation of Crystalline Form II crystals is observed; d) filtering the suspension at a temperature equal to or lower than -5 °C; e) drying the obtained crystalline solid at a temperature above +5 °C, thereby obtaining Drospirenone in Crystalline Form I having fine particle size.
3. Process according to claim 2, wherein step a) is carried out according to a method al) by suspending powders of Drospirenone Crystalline Form I in a mixture of acetone and diisopropyl ether.
4. Process according to claim 2, wherein step a) is carried out according to a method a2) by dissolving powders of Drospirenone, Crystalline Form I or amorphous form, in acetone under reflux conditions, cooling the obtained solution to a temperature comprised between 40 and 45 °C, and adding diisopropyl ether to the cooled solution, carrying out the whole procedure under stirring.
5. Process according to any one of claims 2 to 4, wherein step c) is carried out according to a method cl) by allowing the spontaneous transformation into Crystalline Form II to take place in a time comprised between 0.5 and 48 hours.
6. Process according to claim 5, wherein step c) is carried out according to method cl) at a temperature comprised between -10 and -5 °C for a time comprised between 0.5 and 24 hours.
7. Process according to any one of claims 2 to 4, wherein step c) is carried out according to method c2) by adding a seed of Drospirenone Crystalline Form II to the suspension of step b).
8. Process according to claim 7, wherein step c) according to method c2) is carried out at a temperature comprised between -10 and -5 °C for a time comprised between 0.5 and 2 hours.
9. Process according to any one of claims 7 or 8, wherein a further addition of diisopropyl ether to the suspension is carried out.
10. Process according to any one of claims 2 to 9, wherein step e) is carried out at a temperature comprised between 40 and 50 °C operating at a pressure lower than ambient pressure.
11. Drospirenone Crystalline Form II characterized by an X-ray diffractogram showing diffraction peaks at angular positions of 8.9°, 11.6°, 13.5°, 16.8°, 18.4°, 18.6°, 23.1°, 24.4° and 27.3° ± 0.2° 20.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IT202100000883 | 2021-04-08 | ||
PCT/IB2022/053322 WO2022215048A1 (en) | 2021-04-08 | 2022-04-08 | Process for the preparation of drospirenone as a fine powder through a double change of crystalline form |
Publications (2)
Publication Number | Publication Date |
---|---|
GB202316616D0 GB202316616D0 (en) | 2023-12-13 |
GB2620876A true GB2620876A (en) | 2024-01-24 |
Family
ID=89073539
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB2316616.8A Pending GB2620876A (en) | 2021-04-08 | 2022-04-08 | Process for the preparation of drospirenone as a fine powder through a double change of crystalline form |
Country Status (1)
Country | Link |
---|---|
GB (1) | GB2620876A (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110144071A1 (en) * | 2008-08-08 | 2011-06-16 | Jesalis Pharma Gmbh | Crystalline active ingredient microparticles, method for producing the same and use thereof in drugs |
EP2415778A1 (en) * | 2010-08-03 | 2012-02-08 | Newchem S.p.A. | Methods for the preparation of Drospirenone and intermediates thereof |
-
2022
- 2022-04-08 GB GB2316616.8A patent/GB2620876A/en active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110144071A1 (en) * | 2008-08-08 | 2011-06-16 | Jesalis Pharma Gmbh | Crystalline active ingredient microparticles, method for producing the same and use thereof in drugs |
EP2415778A1 (en) * | 2010-08-03 | 2012-02-08 | Newchem S.p.A. | Methods for the preparation of Drospirenone and intermediates thereof |
Also Published As
Publication number | Publication date |
---|---|
GB202316616D0 (en) | 2023-12-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Wang et al. | Growth mechanism of different morphologies of ZnO crystals prepared by hydrothermal method | |
EP0548114B1 (en) | Mometasone furoate monohydrate, process for making same and pharmaceutical compositions | |
CN110316753B (en) | Hydroxy copper chloride material and synthetic method thereof | |
GB2620876A (en) | Process for the preparation of drospirenone as a fine powder through a double change of crystalline form | |
CN112250440A (en) | Method for preparing low-thermal-conductivity high-temperature thermal barrier ceramic CaWTa2O9 by solid phase method | |
CN105858726B (en) | High yield high-purity MoO2Raw powder's production technology | |
NL2035034B1 (en) | Alumina ceramic and preparation method thereof | |
CN105948012B (en) | Method for preparing β phase tricalcium phosphate crystal material under low temperature condition | |
WO2014012849A1 (en) | A new crystal form of cefoperazone sodium | |
JP2012188325A (en) | Method for producing lanthanum titanate | |
CN111893568B (en) | High-purity NaAlB14Method for producing crystal | |
CN113184924B (en) | Method for preparing high-entropy layered compound by solid phase intercalation method | |
CN115196969A (en) | Solid-phase reaction rapid pressureless sintering method of MgAlON transparent ceramic with high infrared transmittance | |
Ji et al. | Snowflake-like monoclinic VO2 powders: hydrothermal synthesis, characterization and in situ monitoring phase-transition behavior | |
Fadli et al. | Hydroxyapatite powder prepared by low temperature hydrothermal method from sea shells | |
CN104311074A (en) | Sub-micron hercynite, as well as preparation method and application thereof | |
CN114620700B (en) | RbTiOPO 4 Method for preparing nanocrystals | |
Li et al. | Preparation and dieletrical properties of Li 1.075 Nb 0.625 Ti 0.45 O 3 powders by hydrothermal method | |
CN109502636B (en) | Method for preparing electronic grade strontium titanate by solid-liquid mixing spraying method | |
CN112079331B (en) | Synthesis method of metal-nitrogen-hydrogen system hydrogen storage material | |
US20230227323A1 (en) | Salt-assisted phase transformation of transition metal dichalcogenides | |
CN108609656B (en) | Method for simply synthesizing chromium oxide | |
JPS60235797A (en) | Preparation of aluminum orthophosphate crystal | |
JPS62216915A (en) | Production of composite perovskite type compound | |
Zhu et al. | Preparing fluorhydroxyapatite by aqueous precipitation method |